Hepatitis B virus (HBV) infection is a world-wide health problem especially in the Far-East and Africa. A person with chronic HBV infection has 200-fold higher risk of developing hepatocellular carcinoma and cirrhosis as compared to a non-carrier individual. Vaccines for HBV is widely available but for HBV-infected individuals there is no means of arresting the progress of the disease, due in part to our lack of knowledge of how HBV enters the host cells. Recently, several lines of evidence indicated that the pres region of the HBV surface antigen was involved in the direct binding of HBV to human liver cell membranes. In order to obtain large quantities of preS1 peptide, we constructed an expression plasmid for a fusion protein containing beta-galactosidase and preS region of the surface antigen. When such a plasmid was used to transform E. coli, large quantities (greater than 20% of total E. coli protein) of fusion protein was obtained. The preS region was then excised from the fusion protein by Factor Xa cleavage and was purified by mono-Q ion-exchange chromatography. The isolated preS peptide was able to bind specifically to the isolated plasma membranes from human liver and will be used to isolate and characterize receptors on hepatocytes for HBV.